Circadian regulation of estrogen signaling: Toward Chronotherapeutic strategy in menopausal women
Description: Estrogen, and mainly 17ß-estradiol (E2), play a crucial role in physiology for reproduction. Their administration after menopause also confers functional (climacteric symptoms), bone, cardiovascular and metabolic benefits. However, the effects of estrogen on other tissues can be harmful like in breast (cancer risk) and liver (thromboembolic risk) and further investigations are still needed to optimize Hormonal Treatment at menopause (HT) which remains a major issue for women's health. Interestingly, Estrogen Receptor alpha (ERa), considered as the main receptor of estrogen, is expressed with a high amplitude circadian rhythm. Moreover, estrogen signaling is known to regulate some circadian functions in both males and females. However, the molecular mechanisms of circadian expression of ERa are unknown and this aspect of estrogen signaling dynamic is not considered in current therapeutic strategies. Our preliminary results suggest that the circadian expression of ERa is tissue-specific, a clock gene is involved in this regulation and that acute tissue-specific effects of estrogen can be dissociated according to the administration time. Based on these results, we hypothesize that the tissue-specific circadian coordination of estrogen signaling would make it possible to dissociate the protective or adverse chronic effects of estrogens during menopausal hormonal treatment. This project will 1) analyze circadian tissue-specific ERa expression and function; 2) determine the tissue-specific molecular mechanisms underlying the circadian regulation of ERa; and 3) study whether a chronotherapy approach based on this tissue-specific circadian estrogen signaling can optimize hormonal therapies. Altogether, this project aims to study the tissue-specific circadian signaling of ERa to improve the benefit/risk ratio of menopausal hormonal treatment.
Funder: Agence Nationale de la Recherche
Amount: €377,200
Funding type: research
Funder scheme: AAPG2023
Start date: 2023-10-01
Investigator: Marine ADLANMERINI
Institution: Institut des Maladies Métaboliques et Cardiovasculaires
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: ANR-23-CE14-0002
OpenAlex ID: G3010486131